The glypican family has been reported to be a novel family of heparan sulfate proteoglycans present on the cell surface. Five spieces of glypicans (glypican 1, glypican 2, glypican 3, glypican 4, and glypican 5) have been reported as members of the glypican family to date. The members of this family have a core protein of uniform size (approximately 60 kDa), share a unique and highly conserved sequence of cysteines, and are bound to the cell membrane via a glycosylphosphatidylinostiol (GPI) anchor.
Dally (division abnormally delayed) gene was identified by genetic screening of Drosophila melanogaster mutants that had an abnormal cell division pattern during the development of central nervous system. cDNA of Dally has been shown to have an open reading frame (ORF) that codes for a product that exhibits sequence homology (24 to 26% homology) with vertebrate integral membrane proteoglycans (GRIPs) having all the characteristics of glypicans. It was later suggested that Dally plays a role in regulating the dpp (decapentaplegia) receptor mechanism, suggesting the possibility that mammalian glypican modulates TGF and BMP signal transduction. That is, it has been suggested that glypican may function as a coreceptor for some heparin-binding growth factors (e.g., EGF, PDGF, BMP2, FGFs).
Glypican 3 was isolated as a developmentally regulated transcript from the rat small intestine (Filmus, J., Church, J. G., and Buick, R. N. (1988) Mol. Cell. Biol. 8, 4243-4249). It was thereafter identified as OCI-5, a GPI anchored type heparan sulfate proteoglycan of the glypican family having a core protein with a molecular weight of 69 kDa (Filmus, J., Shi, W., Wong, Z.-M., and Wong, M. J. (1995) Biochem. J. 311, 561-565). In humans, a gene encoding glypican 3 has also been isolated as MRX-7 from a human stomach cancer cell line (Hermann Lage et al., Gene 188 (1997) 151-156). Glypican 3 has been reported to form a protein-protein complex with insulin-like growth factor-2 and to regulate the action of this growth factor (Pilia, G. et al. (1996) Nat. Genet. 12, 241-247). This report suggests that glypican 3 does not necessarily interact with growth factors through the heparan sulfate chain.
It has also been reported that glypican 3 may possibly be utilized as a marker of hepatocellular carcinoma (Hey-Chi Hsu et al., Cancer Research 57, 5179-5184 (1997)). Also it has been reported that anti-glypican 3 antibody exhibits a cytotoxic activity against liver cancer cells and may be useful as an anti-cancer agent (WO 03/00883).
However, there have been no reports to the effect that it is possible to use anti-glypican 3 antibody for adjuvant therapy after a cancer treatment.